title: Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia.
abstract: Survival for patients with acute myeloid leukemia (AML) is limited by treatment-related mortality (TRM) and relapse after unrelated donor (URD) hematopoietic cell transplantation (HCT). Natural killer (NK)-cell alloreactivity, determined by donor killer-cell immunoglobulin-like receptors (KIRs) and recipient HLA, correlates with successful HCT for AML. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: at least 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 209 HLA-matched and 239 mismatched T-replete URD transplantations for AML. Three-year overall survival was significantly higher after transplantation from a KIR B/x donor (31% [95% CI: 26-36] vs 20% [95% CI: 13-27]; P = .007). Multivariate analysis demonstrated a 30% improvement in the relative risk of relapse-free survival with B/x donors compared with A/A donors (RR: 0.70 [95% CI: 0.55-0.88]; P = .002). B/x donors were associated with a higher incidence of chronic graft-versus-host disease (GVHD; RR: 1.51 [95% CI: 1.01-2.18]; P = .03), but not of acute GVHD, relapse, or TRM. This analysis demonstrates that unrelated donors with KIR B haplotypes confer significant survival benefit to patients undergoing T-replete HCT for AML. KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes.
authors.affiliation: University of Minnesota, Minneapolis, USA. cool0023@umn.edu
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Bergemann
authors.forename: Koy
authors.initials: K
authors.lastname: Saeteurn
authors.forename: John
authors.initials: J
authors.lastname: Klein
authors.forename: Chap T
authors.initials: CT
authors.lastname: Le
authors.forename: Steven G E
authors.initials: SG
authors.lastname: Marsh
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR